Purpose: To examine the melanocortin receptors (MC-1 through 5) mRNA and the effect of a-melanocyte-stimulating hormone ( a-MSH ) on interleukin-8 (IL-8 ) and monocyte chemotactic protein-1 ( MCP-1) expression in human retinal pigment epithelial cell line (ARPE-19) stimulated with interleukin-16 (IL-16) or tumor necrosis factor-a ( TNF-a ).Methods: MO 1 through 5 mRNA expressions were examined by semiquantitative reverse transcription polymerase chain reaction ( RT-PCR). a-MSH and IL-16 or TNF-a were added to serum-free medium. IL-8 and MCP-1 mRNA were measured by real time PCR. IL-8 and MCP-1 protein concentrations were measured using enzyme-linked immunosorbent assay. Nuclear factor KB ( NF-uB) translocation was examined by immunofluorescence.Results: MC-1 through 5 mRNA were expressed in unstimulated cells. IL-16 stimulated IL-8 and MCP-1 mRNA at 6 hours. TNF-a stimulated IL-8 and MCP-1 mRNA expression at 1.5 hours. a-MSH ( 10 12 -10 8 M ) inhibited IL-8 and MCP-1 mRNA expression in the cells stimulated with IL-16 or TNF-a. a-MSH inhibited IL-16 orTNF-a-stimulated IL-8 and MCP-1 protein levels in the media. Immunofluorescein of NF-KB in the nucleus was dense 30min after stimulation with IL-18 or TNF-a, and was decreased by a-MSH.Conclusions: ARPE-19 ceUs had MC-1 mRNA. a-MSH inhibited IL-8 and MCP-1 expression and protein secretion. Possibly, the effect on chemotactic factors may be via suppression of NF-sB translocation.